Patients with Congenital Factor V Deficiency have Decreased Factor X<sub>a</sub> Binding Sites on their Platelets

Joseph P. Miletich; David W. Majerus; Philip W. Majerus

doi:10.1172/JCI109194

Patients with Congenital Factor V Deficiency have Decreased Factor X_a Binding Sites on their Platelets

Joseph P. Miletich, David W. Majerus, and Philip W. Majerus

Published October 1, 1978 - More info

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Abstract

Human platelets have binding sites for plasma coagulation Factor X_a that are available only after the platelet release reaction. Platelets from 15 normal donors bound 216±52 (SD) molecules of Factor X_a per platelet. The association of Factor X_a with its platelet surface receptor results in a 300,000-fold increase in the catalytic activity of Factor X_a in forming thrombin from prothrombin. The turnover number for platelet-bound Factor X_a was 1,850±460 mol thrombin/ml per min per mol Factor X_a in experiments with platelets from 15 normal donors. Platelets from five patients with varying degrees of Factor V deficiency were investigated to determine whether or not coagulation Factor V participates in either aspect of the Factor X_a-platelet interaction. The binding of Factor X_a to platelets and the accompanying increase in rate of thrombin formation were either reduced in parallel or absent in each case with values ranging from 0 to 45% of control values. The apparent affinity of Factor X_a from Factor V-deficient patients was normal when platelet binding was detected. The supernate from thrombin-treated control platelets, which contains Factor V activity, corrected the Factor X_a binding deficiency of the platelets from three patients tested. Immunoreactive Factor V determined with an homologous antibody corresponded to the functional Factor V activity of platelets from one patient with Factor V deficiency, suggesting that the patient's platelets have a decreased amount of normal Factor V.

The ability of platelets from the patients to bind Factor X_a and increase the rate of thrombin formation correlated with the severity of each patient's bleeding disorder better than the plasma level of Factor V. The results indicate that Factor V is required for the Factor X_a-platelet interaction and that thrombin formation at the platelet surface is important in normal hemostasis.